Visible-Light Cross-Linkable Multifunctional Hydrogels Loaded with Exosomes Facilitate Full-Thickness Skin Defect Wound Healing through Participating in the Entire Healing Process.

The management of severe full-thickness skin defect wounds remains a challenge due to their irregular shape, uncontrollable bleeding, high risk of infection, and prolonged healing period. Herein, an all-in-one OD/GM/QCS@Exo hydrogel was prepared with catechol-modified oxidized hyaluronic acid (OD), methylacrylylated gelatin (GM), and quaternized chitosan (QCS) and loaded with adipose mesenchymal stem cell-derived exosomes (Exos). Cross-linking of the hydrogel was achieved using visible light instead of ultraviolet light irradiation, providing injectability and good biocompatibility. Notably, the incorporation of catechol groups and multicross-linked networks in the hydrogels conferred strong adhesion properties and mechanical strength against external forces such as tensile and compressive stress. Furthermore, our hydrogel exhibited antibacterial, anti-inflammatory, and antioxidant properties along with wound-healing promotion effects. Our results demonstrated that the hydrogel-mediated release of Exos significantly promotes cellular proliferation, migration, and angiogenesis, thereby accelerating skin structure reconstruction and functional recovery during the wound-healing process. Overall, the all-in-one OD/GM/QCS@Exo hydrogel provided a promising therapeutic strategy for the treatment of full-thickness skin defect wounds through actively participating in the entire process of wound healing.

Electrospun Biomimetic Periosteum Capable of Controlled Release of Multiple Agents for Programmed Promoting Bone Regeneration.

The effective repair of large bone defects remains a major challenge due to its limited self-healing capacity. Inspired by the structure and function of the natural periosteum, an electrospun biomimetic periosteum is constructed to programmatically promote bone regeneration using natural bone healing mechanisms. The biomimetic periosteum is composed of a bilayer with an asymmetric structure in which an aligned electrospun poly(ε-caprolactone)/gelatin/deferoxamine (PCL/GEL/DFO) layer mimics the outer fibrous layer of the periosteum, while a random coaxial electrospun PCL/GEL/aspirin (ASP) shell and PCL/silicon nanoparticles (SiNPs) core layer mimics the inner cambial layer. The bilayer controls the release of ASP, DFO, and SiNPs to precisely regulate the inflammatory, angiogenic, and osteogenic phases of bone repair. The random coaxial inner layer can effectively antioxidize, promoting cell recruitment, proliferation, differentiation, and mineralization, while the aligned outer layer can promote angiogenesis and prevent fibroblast infiltration. In particular, different stages of bone repair are modulated in a rat skull defect model to achieve faster and better bone regeneration. The proposed biomimetic periosteum is expected to be a promising candidate for bone defect healing.

Rubropunctatin-silver composite nanoliposomes for eradicating Helicobacter pylori in vitro and in vivo.

Helicobacter pylori (H. pylori) is a major factor in peptic ulcer disease and gastric cancer, and its infection rate is rising globally. The efficacy of traditional antibiotic treatment is less effective, mainly due to bacterial biofilms and the formation of antibiotic resistance. In addition, H. pylori colonizes the gastrointestinal epithelium covered by mucus layers, the drug must penetrate the double barrier of mucus layer and biofilm to reach the infection site and kill H. pylori. The ethanol injection method was used to synthesize nanoliposomes (EPI/R-AgNPs@RHL/PC) with a mixed lipid layer containing rhamnolipids (RHL) and phosphatidylcholine (PC) as a carrier, loaded with the urease inhibitor epiberberine (EPI) and the antimicrobial agent rubropunctatin silver nanoparticles (R-AgNPs). EPI/R-AgNPs@RHL/PC had the appropriate size, negative charge, and acid sensitivity to penetrate mucin-rich mucus layers and achieve acid-responsive drug release. In vitro experiments demonstrated that EPI/R-AgNPs@RHL/PC exhibited good antibacterial activity, effectively inhibited urease activity, removed the mature H. pylori biofilm, and inhibited biofilm regeneration. In vivo antibacterial tests showed that EPI/R-AgNPs@RHL/PC exhibited excellent activity in eradicating H. pylori and protecting the mucosa compared to the traditional clinical triple therapy, providing a new idea for the treatment of H. pylori infection.

Intelligent wound dressing for simultaneous in situ detection and elimination of pathogenic bacteria.

Wound infections hinder the healing process and potentially result in life-threatening complications, which urgently require rapid and timely detection and treatment pathogens during the early stages of infection. Here, an intelligent wound dressing was developed to enable in situ detection and elimination of pathogenic bacteria through a combination of point-of-care testing and antibacterial photodynamic therapy technology. The dressing is an injectable hydrogel composed of carboxymethyl chitosan and oxidized sodium alginate, with addition of 4-methylumphulone beta-D-glucoside (MUG) and up-converted nanoparticles coated with titanium dioxide (UCNPs@TiO2). The presence of bacteria can be visually detected by monitoring the blue fluorescence of 4-methylumbellione, generated through the reaction between MUG and the pathogen-associated enzyme. The UCNPs@TiO2 photosensitizers were synthesized and demonstrated high antibacterial activity through the generation of reactive oxygen species when exposed to near-infrared irradiation. Meanwhile, a smartphone-based portable detection system equipped with a self-developed Android app was constructed for in situ detection of pathogens in mere seconds, detecting as few as 103 colony-forming unit. Additionally, the dressing was tested in a rat infected wound model and showed good antibacterial activity and pro-healing ability. These results suggest that the proposed intelligent wound dressing has potential for use in the diagnosis and management of wound infections. STATEMENT OF SIGNIFICANCE: An intelligent wound dressing has been prepared for simultaneous in situ detection and elimination of pathogenic bacteria. The presence of bacteria can be visually detected by tracking the blue fluorescence of the dressing. Moreover, a smartphone-based detection system was constructed to detect and diagnose pathogenic bacteria before reaching the infection limit. Meanwhile, the dressing was able to effectively eliminate key pathogenic bacteria on demand through antibacterial photodynamic therapy under NIR irradiation. The proposed intelligent wound dressing enables timely detection and treatment of infectious pathogens at an early stage, which is beneficial for wound management.

Chitosan nonwoven fabric composited calcium alginate and adenosine diphosphate as a hemostatic bandage for acute bleeding wounds.

Acute bleeding following accidental injury is a leading cause of mortality. However, conventional hemostatic bandages impede wound healing by inducing excessive blood loss, dehydration, and adherence to granulation tissue. Strategies such as incorporating active hemostatic agents and implementing chemical modifications can augment the properties of these bandages. Nevertheless, the presence of remote thrombosis and initiators may pose risks to human health. Here, a hemostatic bandage was developed by physically combined chitosan nonwoven fabric, calcium alginate sponge, and adenosine diphosphate. The presented hemostatic bandage not only exhibits active and passive mechanisms for promoting clotting but also demonstrates excellent mechanical properties, breathability, ease of removal without causing damage to the wound bed or surrounding tissues, as well as maintaining an optimal moist environment conducive to wound healing. In vitro evaluation results indicated that the hemostatic bandage possesses favorable cytocompatibility with low levels of hemolysis. Furthermore, it effectively aggregates various blood cells while activating platelets synergistically to promote both extrinsic and intrinsic coagulation pathways. In an in vivo rat model study involving liver laceration and femoral artery injury scenarios, our developed hemostatic bandage demonstrated rapid clot formation capabilities along with reduced blood loss compared to commercially available fabrics.

Biomimetic injectable and bilayered hydrogel scaffold based on collagen and chondroitin sulfate for the repair of osteochondral defects.

The simultaneous regeneration of articular cartilage and subchondral bone is a major challenge. Bioinspired scaffolds with distinct regions resembling stratified anatomical architecture provide a potential strategy for osteochondral defect repair. Here, we report the development of an injectable and bilayered hydrogel scaffold with a strong interface binding force. In this bilayer hydrogel, composed of carbonyl hydrazide grafted collagen (COL-CDH) and oxidized chondroitin sulfate (OCS), which are derivatives of osteochondral tissue components, in combination with poly (ethylene glycol) diacrylate (PEGDA), functions as a cartilage layer; while zinc-doped hydroxyapatite acts as a subchondral bone layer that is based on the cartilage layer. The strong interface between the two layers involves dynamic amide bonds formed between COL-CDH and OCS, and permanent CC bonds formed by PEGDA radical reactions. This bilayer hydrogel can be used to inoculate adipose mesenchymal stem cells which can then differentiate into chondrocytes and osteoblasts, secreting glycosaminoglycan, and promoting calcium deposition. This accelerates the regeneration of cartilage and subchondral bone. Micro-CT and tissue staining revealed an increase in the amount of bone present in new subchondral bone, and new tissues with a structure similar to normal cartilage. This study therefore demonstrates that injectable bilayer hydrogels are a promising scaffold for repairing osteochondral defects.

Lecithin/chitosan nanoparticle drug carrier improves anti-tumor efficacy of Monascus pigment rubropunctatin.

Rubropunctatin, a metabolite isolated from the fungi of the genus Monascus, is a natural lead compound applied for the suppression of tumors with good anti-cancer activity. However, its poor aqueous solubility has limited its further clinical development and utilization. Lecithin and chitosan are excellently biocompatible and biodegradable natural materials, which have been approved by the FDA as drug carrier. Here, we report for the first time the construction of a lecithin/chitosan nanoparticle drug carrier of the Monascus pigment rubropunctatin by electrostatic self-assembly between lecithin and chitosan. The nanoparticles are near-spherical with a size 110-120 nm. They are soluble in water and possess excellent homogenization capacity and dispersibility. Our in vitro drug release assay showed a sustained release of rubropunctatin. CCK-8 assays revealed that lecithin/chitosan nanoparticles loaded with rubropunctatin (RCP-NPs) had significantly enhanced cytotoxicity against mouse mammary cancer 4T1 cells. The flow cytometry results revealed that RCP-NPs significantly boosted cellular uptake and apoptosis. The tumor-bearing mice models we developed indicated that RCP-NPs effectively inhibited tumor growth. Our present findings suggest that lecithin/chitosan nanoparticle drug carriers improve the anti-tumor effect of the Monascus pigment rubropunctatin.

Multi-crosslinked hydrogels with strong wet adhesion, self-healing, antibacterial property, reactive oxygen species scavenging activity, and on-demand removability for seawater-immersed wound healing.

In general, seawater-immersed wounds are associated with tissue necrosis, infection, prolonged healing period, and high mortality because of high salinity, hyperosmosis, and the presence of various pathogenic bacteria in seawater. However, current wound dressings can hardly achieve strong and stable wet adhesion and antibacterial properties, thus limiting their application to seawater-immersed wounds. Here a multifunctional hydrogel (OD/EPL@Fe) comprising catechol-modified oxidized hyaluronic acid (OD), ε-poly-L-lysine (EPL), and Fe3+ was prepared primarily through Schiff-base reaction, metal chelation, cation-π, and electrostatic interaction. The hydrogel with high wet adhesion (about 78 kPa) was achieved by combining the mussel-inspired strategy, dehydration effect, and cohesion enhancement, which is higher than that of commercial fibrin glues and cyanoacrylate glues. Meanwhile, the hydrogel can eliminate Marine bacteria (V. vulnificus and P. aeruginosa) and inhibit their biofilm formation. In addition, the hydrogel demonstrated injectability, self-healing, reactive oxygen species scavenging activity, photothermal effect, seawater isolation, on-demand removal, and hemostatic properties. In vivo results showed that the hydrogel had good adhesion to dynamic wounds in a rat neck full-thickness skin wound model. In particular, the hydrogel exhibited antibacterial, anti-inflammatory, and antioxidant properties in a rat seawater-immersed infected wound model and accelerated the reconstruction of skin structure and functions. The results demonstrated that the OD/EPL@Fe would be a potential wound dressing for seawater-immersed wound healing. STATEMENT OF SIGNIFICANCE: A multifunctional OD/EPL@Fe hydrogel has been prepared for the treatment of seawater-immersed wounds. The hydrogel with high wet adhesion was achieved by combining the mussel-inspired strategy, dehydration effect, and cohesion enhancement. The results revealed that the wet adhesion value of hydrogel was about eight times greater than commercial fibrin glues and 1.5 times greater than commercial cyanoacrylate glues. The hydrogel can be easily removed after being sprayed with deferoxamine mesylate. Notably, the inherent antimicrobial material of the hydrogel combined with the photothermal effect can eliminate marine bacteria and inhibit their biofilm formation. Moreover, the hydrogel can accelerate the healing of seawater-immersed infected wound on mice.

Biomimetic multifunctional hybrid sponge via enzymatic cross-linking to accelerate infected burn wound healing.

Preparing sponge dressings with stable wet adhesion remains difficult in wound repair, especially in burn wounds with bleeding and large amounts of exudate. In this work, a multifunctional hybrid sponge dressing (DHGT+PHMB+TiO2NPs) with good wet adhesion was developed by combining biomimetic and enzymatic cross-linking reactions. The sponge dressing matrix (DHGT) was prepared by tyrosinase-catalyzed cross-linking of dopamine-modified hyaluronic acid (DOPA-HA) and gelatin. The multifunctional hybrid sponge dressing was obtained by loading polyhexamethylene biguanide (PHMB) and titanium dioxide nanoparticles (TiO2NPs) onto the DHGT matrix. The newly developed sponge dressing exhibited high mechanical properties, good wet adhesion, antibacterial activity, reactive oxygen species (ROS) scavenging, biocompatibility, and excellent hemostasis ability. In vivo studies showed that the multifunctional hybrid sponge dressing could significantly accelerate the healing of infected full-thickness burn wounds by inhibiting bacterial growth, accelerating skin tissue reepithelialization, collagen deposition, and angiogenesis, as well as regulating the expression of inflammatory factors and cytokines.

Eco-Friendly Green Synthesis of Rubropunctatin Functionalized Silver Nanoparticles and Evaluation of Antibacterial Activity.

In order to solve the problems of rubropunctatin insoluble in water and its low bioavailability, and explore the synthesis method of green silver nanoparticles, rubropunctatin was used as reducing agent and blocking agent, rubropunctatin-functionalized silver nanoparticles (R-AgNPs) were successfully synthesized. The distinctive absorption peak at 410 nm confirmed the formation of R-AgNPs. Zeta potential measurement showed excellent stability of R-AgNPs with negative values of -29.81 ± 0.37 mV. The results of TEM and XRD showed that the prepared R-AgNPs were round, well dispersed and crystallized with average particle size of 13.54 ± 0.42 nm. FT-IR and XPS studies show that functional groups are involved in R-AgNPs synthesis. The antibacterial activity of R-AgNPs was compared with commercial silver nanoparticles (AgNPs) by microdilution method. The results showed that R-AgNPs (MIC 7.81 µg/mL) has stronger antibacterial activity than commercial AgNPs. The bacteria morphology was observed by the live and dead (SYTO 9/PI) staining assay and SEM showed that the antibacterial effect of R-AgNPs was caused by the destruction of the bacterial cell membrane. Cytotoxicity of rubropunctatin-functionalized silver nanoparticles and commercial silver nanoparticles on mouse fibroblast 3T3 cells was assessed by CCK-8 assay. The results showed that the toxicity of rubropunctatin-functionalized silver nanoparticles to 3T3 cells was lower than that of commercial silver nanoparticles. In summary, synthesis of silver nanoparticles using rubropunctatin is a green synthesis method, and R-AgNPs is a potential antibacterial agent.

Biomimetic Asymmetric Composite Dressing by Electrospinning with Aligned Nanofibrous and Micropatterned Structures for Severe Burn Wound Healing.

The surface structure and topography of biomaterials play a crucial role in directing cell behaviors and fates. Meanwhile, asymmetric dressings that mimic the natural skin structure have been identified as an effective strategy for enhancing wound healing. Inspired by the skin structure and the superhydrophobic structure of the lotus leaf, an asymmetric composite dressing was obtained by constructing an asymmetric structure and wettability surface modification on both sides of the sponge based on electrospinning. Among them, the collagen and quaternized chitosan sponge was fabricated by freeze-drying, followed by an aligned poly(ε-caprolactone) (PCL)/gelatin nanofiber hydrophilic inner layer and hierarchical micronanostructure PCL/polystyrene microsphere highly hydrophobic outer layer constructed on each side of the sponge. The proposed asymmetric composite dressing combines topological morphology with the material's properties to effectively prevent bacterial colonization/infection and promote wound healing by directing cellular behavior. In vitro experimental results confirmed that the aligned nanofiber inner layer effectively promotes cell adhesion, proliferation, directed cell growth, and migration. Meanwhile, the sponge has good water absorption and antibacterial properties, while the biomimetic hydrophobic outer layer exhibits strong mechanical properties and resistance to bacterial adhesion. In vivo results showed that the composite dressing can reduce inflammatory response, prevent infection, accelerate angiogenesis and epithelial regeneration, and significantly accelerate the healing of severe burns. Thus, the proposed bionic asymmetric dressing is expected to be a promising candidate for severe burn wound healing.

An injectable double network hydrogel with hemostasis and antibacterial activity for promoting multidrug-resistant bacteria infected wound healing.

Multidrug-resistant bacteria infections frequently occur in wound care due to the excessive use of antibiotics. It can cause scar formation, wound closure delay, multiple organ failure, and high mortality. Here, a double network hydrogel with injectability, hemostasis, and antibacterial activity was developed to prompt multidrug-resistant bacteria infected wound healing. The double network hydrogel is composed of gelatin methacryloyl (GelMA), oxidized dextran (ODex), ε-polylysine (EPL), and bacitracin, and formed through the Schiff-base and UV-initiated crosslinking reaction. The injectable hydrogel with an adhesion effect could adapt to the irregular shape of the wound and possesses good hemostatic ability. The hydrogel presents good flexibility and rapid resilience due to its double network structure, and it can prompt cell proliferation and migration. In particular, the hydrogel has broad-spectrum in vitro antimicrobial activities against S. aureus, E. coli, and methicillin-resistant S. aureus (MRSA), and disrupts E. coli and MRSA biofilms. In vivo results demonstrated that the hydrogel can completely heal MRSA-infected wound in rats within 15 days, through inhibiting the growth of bacteria, accelerating skin tissue reepithelialization, collagen deposition, and angiogenesis, as well as adjusting the expression of CD31, α-SMA, and TNF-α. The findings of this study suggest that the presented hydrogel could enhance multidrug-resistant bacteria infected wound healing and mitigate antimicrobial resistance.

A sandwich structure composite wound dressing with firmly anchored silver nanoparticles for severe burn wound healing in a porcine model.

Wounds may remain open for a few weeks in severe burns, which provide an entry point for pathogens and microorganisms invading. Thus, wound dressings with long-term antimicrobial activity are crucial for severe burn wound healing. Here, a sandwich structure composite wound dressing anchored with silver nanoparticles (AgNPs) was developed for severe burn wound healing. AgNPs were in situ synthesized on the fibers of chitosan nonwoven fabric (CSNWF) as the interlayer of wound dressing for sustained release of silver ion. The firmly anchored AgNPs could prevent its entry into the body, thereby eliminating the toxicity of nanomaterials. The outer layer was a polyurethane membrane, which has a nanoporous structure that could maintain free transmission of water vapor. Chitosan/collagen sponge was selected as the inner layer because of its excellent biocompatibility and biodegradability. The presence of AgNPs in the CSNWF was fully characterized, and the high antibacterial activity of CSNWF/AgNPs was confirmed by against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The superior wound healing effect on deep dermal burns of presented composite wound dressing was demonstrated in a porcine model. Our finding suggested that the prepared AgNPs doped sandwich structure composite wound dressing has great potential application in severe wound care.

A Nomogram for Predicting Risk of Thromboembolism in Gastric Cancer Patients Receiving Chemotherapy.

Purpose: The aims of this study were to develop and validate a novel nomogram to predict thromboembolism (TE) in gastric cancer (GC) patients receiving chemotherapy and to test its predictive ability. Methods: This retrospective study included 544 GC patients who received chemotherapy as the initial treatment at two medical centers. Among the 544 GC patients who received chemotherapy, 275 and 137 patients in the First Affiliated Hospital of Nanchang University from January 2014 to March 2019 were enrolled in the training cohort and the validation cohort, respectively. A total of 132 patients in the Beilun branch of the First Affiliated Hospital of Zhejiang University from January 2015 to August 2019 were enrolled in external validation cohorts. The nomogram was based on parameters determined by univariate and multivariate logistic analyses. The prediction performance of the nomogram was measured by the area under the receiver operating characteristic curve (AUROC), the calibration curve, and decision curve analysis (DCA). The applicability of the nomogram was internally and independently validated. Results: The predictors included the Eastern Cooperative Oncology Group Performance Status (ECOG), presence of an active cancer (AC), central venous catheter (CVC), and D-dimer levels. These risk factors are shown on the nomogram and verified. The nomogram demonstrated good discrimination and fine calibration with an AUROC of 0.875 (0.832 in internal validation and 0.807 in independent validation). The DCA revealed that the nomogram had a high clinical application value. Conclusions: We propose the nomogram for predicting TE in patients with GC receiving chemotherapy, which can help in making timely personalized clinical decisions for different risk populations.

Smartphone-based reading system integrated with phycocyanin-enhanced latex nanospheres immunoassay for on-site determination of aflatoxin B1 in foodstuffs.

Traditional methods for aflatoxin B1 (AFB1) detection are complex, time-consuming, labor-intensive, and high cost. Moreover, they require sophisticated large-scale instrumentation, which limits their on-site rapid detection. Herein, phycocyanin fluorescent nanospheres based on fluorescence immunochromatographic assay were developed for quantitative detection of AFB1 at parts-per-billion (ppb) levels in foodstuffs. Phycocyanin and anti-AFB1 monoclonal antibodies were coupled on the surface of latex nanospheres to amplify the fluorescence signal and improve the sensitivity. The fluorescence intensity was measured by a self-developed smartphone-based reading system. Under the optimal conditions, this approach achieved quantitative point-of-care detection of AFB1 within 25 min. The calibration curve for AFB1 was linear in the range of 0.2-48 ppb, and the limit of detection was 0.16 ppb. The practical applicability of the proposed approach was demonstrated by the determination of AFB1 in naturally contaminated samples, and the results were consistent with HPLC detection.

Characterization and biological evaluation of a novel silver nanoparticle-loaded collagen-chitosan dressing.

Effective coverage and protection is a priority in wound treatment. Collagen and chitosan have been widely used for wound dressings due to their excellent biological activity and biocompatibility. Silver nanoparticles (AgNPs) have a powerful antibacterial effect. In this study, a macromolecular and small-molecular collagen mixed solution, a macromolecular and small-molecular chitosan mixed solution were prepared, and a silver nanoparticle-loaded collagen-chitosan dressing (AgNP-CCD) has been proposed. First, the effects of a collagen-chitosan mixed solution on the proliferation of human umbilical vein endothelial cells and the secretion of cytokines were evaluated. Then, the characteristics and antibacterial effects of the AgNP-CCD were tested, and the effects on wound healing and the influence of wound cytokine expression were investigated via a deep second-degree burn wound model. The results showed that at the proper proportion and concentration, the collagen-chitosan mixed solution effectively promoted cell proliferation and regulated the levels of growth factors (vascular endothelial growth factor [VEGF], epidermal growth factor [EGF], platelet-derived growth factor [PDGF], transforming growth factor [TGF-ß1], basic fibroblastic growth factor [bFGF]) and inflammatory factors (TNF-α, IL-1ß, IL-6, IL-8). Moreover, AgNP solutions at lower concentrations exerted limited inhibitory effects on cell proliferation and had no effect on cytokine secretion. The AgNP-CCD demonstrated satisfactory morphological and physical properties as well as efficient antibacterial activities. An in vivo evaluation indicated that AgNP-CCD could accelerate the healing process of deep second-degree burn wounds and played an important role in the regulation of growth and inflammatory factors, including VEGF, EGFL-7, TGF-ß1, bFGF, TNF-α and IL-1ß. This AgNP-CCD exerted excellent biological effects on wound healing promotion and cytokine expression regulation.

Preparation of aminated fish scale collagen and oxidized sodium alginate hybrid hydrogel for enhanced full-thickness wound healing.

Acute full-thickness wounds require a more extended healing period, thus increasing the risk of infection. Severe infection frequently resulted in wound ulceration, necrosis, and even life-threatening complications. Here, a hybrid hydrogel comprising aminated collagen (AC), oxidized sodium alginate (OSA), and antimicrobial peptides (polymyxin B sulfate and bacitracin) was developed to enhance full-thickness wound healing. The AC with low immunogenicity and high biocompatibility was made from marine fish scales, which are eco-friendly, low-cost, and sustainable. The cross-linked hydrogel was formed by a Schiff base reaction without any catalysts and additional procedures. As expected, the presented hybrid hydrogel can effectively against E. coli and S. aureus, as well as promote cell growth and angiogenesis in vitro. In addition, the hydrogel can promote full-thickness wound healing in a rat model through accelerating reepithelialization, collagen deposition, and angiogenesis. Our work demonstrated that the hybrid hydrogel has promising applications in the field of wound healing, which would prompt the utilization of marine fish resources during food processing.

Preparation and evaluation of a Rubropunctatin-loaded liposome anticancer drug carrier.

Rubropunctatin is a naturally occurring constituent of polyketide compounds that has great potential in the development of cancer-assisted chemotherapy. However, it has certain shortcomings such as water insolubility and photo instability that limit its clinical application. In this study, we constructed a Rubropunctatin-loaded liposome (R-Liposome) anticancer drug carrier for the first time. The results indicate that R-Liposome is water soluble, has spherical morphology, great homogeneity and dispersibility with high encapsulation efficiency (EE%, 90 ± 3.5%) and loading rate (LR%, 5.60 ± 2.5%) values. Moreover, the carrier improves the photostability, storage and pH stabilities of Rubropunctatin. The R-Liposome also prolongs the release of Rubropunctatin, enhances the anticancer activity of Rubropunctatin and encourages the mechanism of Rubropunctatin to promote apoptosis. Therefore, liposomal nanoparticles have great potential as drug delivery vehicles of Rubropunctatin for cancer treatment.

Asymmetric Wettable Composite Wound Dressing Prepared by Electrospinning with Bioinspired Micropatterning Enhances Diabetic Wound Healing.

Wound dressings with asymmetric wettability surfaces can effectively prevent bacterial colonization and tissue dehydration and have shown great potential for diabetic wound healing applications. However, the construction of a highly hydrophobic outer surface with high biocompatibility and permeability is still the major challenge in the preparation of asymmetric wettable dressings. Inspired by the superhydrophobic surface structures existing in nature, an asymmetric wettable composite wound dressing with a highly hydrophobic outer layer was successfully prepared for diabetic wound healing in this study. The hydrophobic outer layer was fabricated by the electrospinning of poly(ε-caprolactone) (PCL) on a micron-pore-size nylon mesh template, and the hydrophilic inner layer was obtained by the electrospinning of pioglitazone-incorporated gelatin (Gel-pio). The hydrophobic outer layer of the dressing with a hierarchical micro-nanostructure exhibits excellent ability to waterproof and prevent bacterial adhesion, whereas the hydrophilic inner layer can promote cell proliferation, migration, and angiogenesis by its nanofiber structure and biocompatible gelatin composition. The presented dressing has good mechanical properties, permeability, and high biocompatibility. More importantly, the results of full-thickness skin wound model evaluation on db/db mice (type 2 diabetes) and STZ rats (type 1 diabetes) indicate that the developed dressing can promote wound healing by stimulating cell proliferation, angiogenesis, collagen deposition, and re-epithelialization. The findings of this study suggest that the bioinspired asymmetric wettable composite wound dressing can be used as a promising candidate for diabetic wound healing.

Transglutaminase-Catalyzed Encapsulation of Individual Mammalian Cells with Biocompatible and Cytoprotective Gelatin Nanoshells.

Mammalian cells are extremely vulnerable to external assaults compared with plant and microbial cells because of the weakness of cell membranes compared with cell walls. Construction of ultrathin and robust artificial shells on mammalian cells with biocompatible materials is a promising strategy for protecting single cells against harsh environmental conditions. Herein, layer-by-layer assembly combined with a transglutaminase-catalyzed cross-linking reaction was employed to prepare cross-linked and biocompatible gelatin nanoshells on individual human cervical carcinoma cell line (HeLa) cells and mouse insulinoma cell line 6 (MIN6) cells. The encapsulated HeLa and MIN6 cells showed high viability and a prolonged encapsulation period. Moreover, the nanoshells can protect encapsulated cells from cytotoxic enzymes (such as trypsin) and polycation (polyethylenimine) attacks and help cells resist high physical stress. We also investigated how nanoshells would affect the cell viability, proliferation, and cell cycle distribution of encapsulated and released cells. The approach presented here may provide a new and versatile method for nanoencapsulation of individual mammalian cells, which would help cells endure various environmental stresses and thereby expand the application field of isolated mammalian cells.